Artikel
The dopaminergic pathway – a potential new way to target B cells in rheumatic diseases
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Veröffentlicht: | 8. Oktober 2019 |
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Gliederung
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Background: Dopamine (DA) is involved in local joint inflammation of rheumatoid arthritis (RA) patients. Moreover, limited studies already address its pro-inflammatory role for systemic immune responses, specifically in autoimmunity. By examining the dopaminergic system and its function in peripheral blood mononuclear cells (PBMCs) of healthy controls (HC) and rheumatic diseased patients we looked for disease-related alterations. Thereby, we aim to reveal new possible targets within the dopaminergic pathway for directed therapy of rheumatic diseases.
Methods: Expression of DA receptors (DRD1-5) was investigated via flow cytometry in PBMCs of HC (n = 14-17) and patients diagnosed with RA (n = 11-17), psoriasis arthritis (PsA, n = 12-14) and spondylitis ankylosans (SpA, n = 15-19). Expression data was correlated with age, gender and clinical features. To evaluate DA function specifically for B cells in vitro, we used DR agonists alongside either T cell-dependent or -independent stimulatory conditions.
Results: All investigated subpopulations of PBMCs express DRs and we also found some gender-dependent variations in expression levels. The expression levels of DRD1-5 in immune cells of PsA, as well as SpA are similar to HC. B cells of RA patients expressed significantly higher levels of DRD1 than HC (P = 0,03), but particularly this increased expression originated only from women affected by RA compared to HC (p = 0,0007). Moreover, in female patients the expression of DRD1 correlated with disease duration (p = 0,0046) and functional impairment (p = 0,008). First results of in vitro experiments suggest a DA-mediated regulation of B cell maturation.
Conclusion: Targeted modulation of overexpressed DRs could be a way to suppress pro-inflammatory effects of autoantibody-producing B cells in RA. More functional analysis are ongoing to better define DA role in systemic immune response in rheumatic diseases. Consideration of the neuro-immune axis as a new way for treatment of rheumatic diseases seems worthwhile.